Mutations in the X-linked hematopoietic transcription factor, GATA-1, have been associated with dyserythropoietic anemia, congenital erythropoietic porphyria and macrothrombocytopenia. Earlier we described the platelet pathology in 3 male members of a previously reported (

Mehaffey M.G. et all:
Blood
.
2001
;
98
:
2681
–2688
) family with the GATA-1 G208S mutation and serious bleeding problems. All were found to have giant hypogranular platelets with frequent tubular inclusions, parallel associated double membrane sheets connected to channels of the surface connected open canalicular system (OCS), platelets in platelets, and platelets attached to platelets. Their platelets spread normally on formvar grids, but the ability to bind von Willebrand factor (vWF) was half that of normal controls and limited to small multimers rather than the cargo net of large multimers bound by normal platelets. The present study has focused on platelets from four possible female carriers of the GATA-1 mutation in this family. All four of the women have had mild bleeding symptoms, close to normal platelet counts, slight increases in MPV, but no platelet abnormalities on peripheral blood smears. Thin sections of their platelets examined in the electron microscope revealed features consistent with the pathology observed in male family members. Most of their platelets were normal-sized, discoid cells containing the usual complement of alpha and delta storage organelles and channels of the dense tubular system and OCS. However, a significant member of giant platelets containing the usual frequency of alpha and delta granules and hypogranular and agranular giant platelets were observed. The frequency of the macrothrombocytes varied in each of the four women studied, but were present in all. The ability of their platelets to bind multimers of vWF, in contrast to male family members, did not differ from normal controls. Near normal as well as normal platelet counts and the ability of their platelets to bind vWF multimers may protect them from the serious bleeding problems of males with the X-linked GATA-1 G208S mutation. Our findings indicate that obligate female carriers of the GATA-1 gene can be detected by examination of their platelets in the electron microscope.

Disclosure: No relevant conflicts of interest to declare.